Zach Heidemarie, Dirkx Michiel F, Pasman Jaco W, Bloem Bastiaan R, Helmich Rick C
Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands.
Department of Neurology, Medical University of Vienna, Vienna, Austria.
CNS Neurosci Ther. 2017 Mar;23(3):209-215. doi: 10.1111/cns.12670. Epub 2017 Jan 10.
Resting tremor in Parkinson's disease (PD) increases markedly during cognitive stress. Dopamine depletion in the basal ganglia is involved in the pathophysiology of resting tremor, but it is unclear whether this contribution is altered under cognitive stress. We test the hypothesis that cognitive stress modulates the levodopa effect on resting tremor.
Tremulous PD patients (n = 69) were measured in two treatment conditions (OFF vs. ON levodopa) and in two behavioral contexts (rest vs. cognitive co-activation). Using accelerometry, we tested the effect of both interventions on tremor intensity and tremor variability.
Levodopa significantly reduced tremor intensity (across behavioral contexts), while cognitive co-activation increased it (across treatment conditions). Crucially, the levodopa effect was significantly smaller during cognitive co-activation than during rest. Resting tremor variability increased after levodopa and decreased during cognitive co-activation.
Cognitive stress reduces the levodopa effect on Parkinson's tremor. This effect may be explained by a stress-related depletion of dopamine in the basal ganglia motor circuit, by stress-related involvement of nondopaminergic mechanisms in tremor (e.g., noradrenaline), or both. Targeting these mechanisms may open new windows for treatment. Clinical tremor assessments under evoked cognitive stress (e.g., counting tasks) may avoid overestimation of treatment effects in real life.
帕金森病（PD）患者的静止性震颤在认知应激期间会显著增加。基底神经节中的多巴胺耗竭参与了静止性震颤的病理生理学过程，但尚不清楚这种作用在认知应激下是否会发生改变。我们检验了认知应激会调节左旋多巴对静止性震颤作用的假设。
对震颤型PD患者（n = 69）在两种治疗状态（未服用左旋多巴与服用左旋多巴）和两种行为情境（休息与认知共激活）下进行测量。使用加速度计，我们测试了这两种干预对震颤强度和震颤变异性的影响。
左旋多巴显著降低了震颤强度（在各种行为情境下），而认知共激活则增加了震颤强度（在各种治疗状态下）。至关重要的是，认知共激活期间左旋多巴的作用明显小于休息期间。左旋多巴治疗后静止性震颤变异性增加，而在认知共激活期间降低。
认知应激会降低左旋多巴对帕金森震颤的作用。这种作用可能是由于基底神经节运动回路中与应激相关的多巴胺耗竭，或是由于与应激相关的非多巴胺能机制（如去甲肾上腺素）参与震颤，或两者兼而有之。针对这些机制可能会为治疗打开新的窗口。在诱发认知应激（如计数任务）下进行临床震颤评估可能会避免在现实生活中高估治疗效果。
